Carcinogenicity assays of trichloroethylene (TCE), tetrachloroethylene (PCE) and related halogenated hydrocarbons have resulted in equivocal findings. Chloroform (CHCl3) and carbon tetrachloride (CCl4) are both "weak carcinogens" and they have been shown to yield carbonyl chloride in in vitro experiments. This present proposal deals with the mode of action of CHCl3 and CCl4. The proposed studies will deal with their interactions with rat liver chromatin and its component macromolecules. The purpose of these biochemical studies will be to determine whether carbonyl chloride is their common activated carcinogenic intermediate. The possibility that CHCl3 and CCl4 are tumor promoters or cocarcinogens will be explored by bioassays in mice and rats. These proposed studies should shed new light on the mode of action of these and other halogenated hydrocarbons such as TCE and PCE. All of these agents are extensively used and become widely dispersed in the environment; hence, more information on their metabolism, carcinogeeic and/or promoting and cocarcinogenic action is of great importance.